This application addresses broad Challenge Area (13) Smart Biomaterials-Theranostics and specific Challenge Topic, 13-DE-102: Dental Resin Composite and Caries. It is known that half of all dental restorations fail within 10 years and replacing them consumes 60% of the average dentist's practice time. Secondary caries and fracture of the restoration are found to be the main reasons for restoration failure. To face these challenges, dental restoratives must be made strong and stable enough to withstand fracture and wear, and antibacterial enough to prevent or reduce secondary caries. The overall goal of this research project is to develop a novel high-performance biocompatible glass-ionomer cement (GIC) system with permanent antibacterial function to combat bacterial destruction, prevent biofilm formation and withstand fracture and wear for enhancing restoration longevity. Currently, none of the commercially available GICs are being used for high stress- and high wear-bearing restorations as are composite resins, due to their poor wear-resistance and low mechanical strengths, although these cements have numerous advantages over composite resins. Furthermore, none of the dental restoratives are permanently antibacterial, which significantly increases the incidence of secondary caries. We have demonstrated that novel star-shaped polyacid-constructed resin-modified GIC (RMGIC) exhibited outstanding and comparable wear-resistance as well as mechanical strengths to some of the current composite resins, in addition to its inherent adhesion to tooth that composite resins do not have. In this challenge proposal, we propose to develop a novel antibacterial and biocompatible high-performance RMGIC system constructed with well- designed highly-branched polymers along with covalently attached quaternary ammonium cations (Quats) for stronger and longer-lasting restoration as well as secondary cavity prevention or reduction. This system is uniquely designed to combine all the major advantages but minimize the disadvantages that composite resins, conventional GICs and RMGICs have. In this research, a series of well-designed as well as well- constructed highly-branched polymers and a series of new antibacterial Quats will be synthesized and used to formulate a high-performance GIC system with permanent antibacterial function. Flexural strength, wear- resistance and viscosity will be used as primary screening tools for cement formulation and optimization. Bactericidal testing against Streptococcus mutans will be used as a primary screening tool for Quat's antibacterial evaluation. Important mechanical properties, physical properties, in vitro antibacterial activity and in vitro biocompatibility of the optimal system will be evaluated. Successful achievement of the goals of this project will positively impact the fields of restorative, preventive and minimally invasive dentistry and early caries intervention by providing a new attractive antibacterial adhesive dental restorative. Secondary caries and fracture of the restoration are found to be the main reasons for dental restoration failure. To face these challenges, dental restoratives must be made strong and stable enough to withstand fracture and wear, and antibacterial enough to prevent or reduce secondary caries. The objective of this research is to develop a novel high-performance biocompatible glass-ionomer cement system with permanent antibacterial function to combat bacterial destruction, prevent biofilm formation and withstand fracture and wear for enhancing restoration longevity.